Schematic overview of the cellular and molecular mechanisms involved in the cancer progression, including the proposed cellular and molecular mechanisms in cancer cells trajectory. AT1: alveolar type 1 cells; AT2: alveolar type 2 cells; AAH: atypical adenomatous hyperplasia; AIS: adenocarcinoma in situ; MIA: minimally invasive adenocarcinoma; IA: invasive adenocarcinoma; EMT: epithelial-mesenchymal transition

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	Gene summary
	Malignant transformation analysis
	Malignant transformation related pathway analysis
	Cell-cell communication analysis
	Single-cell gene regulatory network inference analysis
	Somatic mutation of malignant transformation related genes
	Related drugs of malignant transformation related genes

Gene: DAZAP1

Gene summary for DAZAP1

Gene summary.

Gene information	Species	Human
	Gene symbol	DAZAP1
	Gene ID	26528
	Gene name	DAZ associated protein 1
	Gene Alias	DAZAP1
	Cytomap	19p13.3
	Gene Type	protein-coding
	GO ID	GO:0000003
	UniProtAcc	A0A0S2Z569

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Malignant transformation analysis

Identification of the aberrant gene expression in precancerous and cancerous lesions by comparing the gene expression of stem-like cells in diseased tissues with normal stem cells

Malignant transformation involving gene list.

Entrez ID	Symbol	Replicates	Species	Organ	Tissue	Adj P-value	Log2FC	Malignancy
26528	DAZAP1	HTA11_3410_2000001011	Human	Colorectum	AD	2.83e-02	6.47e-02	0.0155
26528	DAZAP1	HTA11_347_2000001011	Human	Colorectum	AD	2.06e-06	3.00e-01	-0.1954
26528	DAZAP1	HTA11_1391_2000001011	Human	Colorectum	AD	2.60e-05	4.79e-01	-0.059
26528	DAZAP1	HTA11_7862_2000001011	Human	Colorectum	AD	2.65e-02	3.91e-01	-0.0179
26528	DAZAP1	HTA11_99999970781_79442	Human	Colorectum	MSS	1.75e-05	4.30e-01	0.294
26528	DAZAP1	HTA11_99999971662_82457	Human	Colorectum	MSS	2.75e-12	6.77e-01	0.3859
26528	DAZAP1	A015-C-203	Human	Colorectum	FAP	6.94e-06	2.58e-02	-0.1294
26528	DAZAP1	A002-C-205	Human	Colorectum	FAP	8.56e-04	-2.23e-01	-0.1236
26528	DAZAP1	A015-C-106	Human	Colorectum	FAP	2.60e-02	2.11e-02	-0.0511
26528	DAZAP1	A015-C-104	Human	Colorectum	FAP	9.06e-07	-2.73e-02	-0.1899
26528	DAZAP1	A002-C-016	Human	Colorectum	FAP	2.32e-04	-8.14e-02	0.0521
26528	DAZAP1	A002-C-116	Human	Colorectum	FAP	1.34e-09	-2.11e-01	-0.0452
26528	DAZAP1	F034	Human	Colorectum	FAP	1.93e-04	-1.03e-01	-0.0665
26528	DAZAP1	LZE2T	Human	Esophagus	ESCC	3.40e-05	4.46e-01	0.082
26528	DAZAP1	LZE4T	Human	Esophagus	ESCC	4.47e-04	-9.87e-03	0.0811
26528	DAZAP1	LZE5T	Human	Esophagus	ESCC	1.79e-03	1.46e-01	0.0514
26528	DAZAP1	LZE7T	Human	Esophagus	ESCC	1.70e-06	3.44e-01	0.0667
26528	DAZAP1	LZE20T	Human	Esophagus	ESCC	1.92e-08	6.76e-02	0.0662
26528	DAZAP1	LZE22D1	Human	Esophagus	HGIN	1.15e-04	5.74e-02	0.0595
26528	DAZAP1	LZE22T	Human	Esophagus	ESCC	5.10e-07	2.79e-01	0.068

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Transcriptomic changes along malignancy continuum.

Tissue	Expression Dynamics	Abbreviation
Colorectum (GSE201348)		FAP: Familial adenomatous polyposis
		CRC: Colorectal cancer
Colorectum (HTA11)		AD: Adenomas
		SER: Sessile serrated lesions
		MSI-H: Microsatellite-high colorectal cancer
		MSS: Microsatellite stable colorectal cancer
Esophagus		ESCC: Esophageal squamous cell carcinoma
		HGIN: High-grade intraepithelial neoplasias
		LGIN: Low-grade intraepithelial neoplasias
Liver		HCC: Hepatocellular carcinoma
		NAFLD: Non-alcoholic fatty liver disease
Oral Cavity		EOLP: Erosive Oral lichen planus
		LP: leukoplakia
		NEOLP: Non-erosive oral lichen planus
		OSCC: Oral squamous cell carcinoma
Skin		AK: Actinic keratosis
		cSCC: Cutaneous squamous cell carcinoma
		SCCIS:squamous cell carcinoma in situ
Thyroid		ATC: Anaplastic thyroid cancer
		HT: Hashimoto's thyroiditis
		PTC: Papillary thyroid cancer

∗log2FC in expression of this searched gene in stem-like cells from each diseased tissue sample relative to stem-like cells in normal samples in each tissue plotted against the malignancy continuum. Samples are colored based on if they are from different disease stage.

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Malignant transformation related pathway analysis

Find out the enriched GO biological processes and KEGG pathways involved in transition from healthy to precancer to cancer

Figure of enriched GO biological processes.

Tissue	Disease Stage	Enriched GO biological Processes
Colorectum	AD
Colorectum	SER
Colorectum	MSS
Colorectum	MSI-H
Colorectum	FAP

∗Top 15 enriched GO BP terms are showed in the bar plot of each disease state in each tissue. Each row represents a significant GO biological process which is colored according to the -log10(p.adjust).

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Enriched GO biological processes.

GO ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	Count
GO:004348412	Liver	Cirrhotic	regulation of RNA splicing	85/4634	148/18723	2.03e-17	2.83e-15	85
GO:004802412	Liver	Cirrhotic	regulation of mRNA splicing, via spliceosome	62/4634	101/18723	5.83e-15	6.20e-13	62
GO:190331311	Liver	Cirrhotic	positive regulation of mRNA metabolic process	56/4634	118/18723	7.05e-08	2.14e-06	56
GO:00331205	Liver	Cirrhotic	positive regulation of RNA splicing	24/4634	37/18723	2.87e-07	7.01e-06	24
GO:0050685	Liver	Cirrhotic	positive regulation of mRNA processing	20/4634	32/18723	6.64e-06	1.04e-04	20
GO:00480265	Liver	Cirrhotic	positive regulation of mRNA splicing, via spliceosome	15/4634	22/18723	2.14e-05	2.81e-04	15
GO:00018905	Liver	Cirrhotic	placenta development	57/4634	144/18723	5.74e-05	6.58e-04	57
GO:00614585	Liver	Cirrhotic	reproductive system development	132/4634	427/18723	2.07e-03	1.28e-02	132
GO:00486085	Liver	Cirrhotic	reproductive structure development	131/4634	424/18723	2.19e-03	1.34e-02	131
GO:0007565	Liver	Cirrhotic	female pregnancy	65/4634	193/18723	3.21e-03	1.80e-02	65
GO:00018932	Liver	Cirrhotic	maternal placenta development	16/4634	35/18723	5.53e-03	2.80e-02	16
GO:0044706	Liver	Cirrhotic	multi-multicellular organism process	70/4634	220/18723	1.03e-02	4.61e-02	70
GO:0060135	Liver	Cirrhotic	maternal process involved in female pregnancy	24/4634	62/18723	1.03e-02	4.61e-02	24
GO:000838022	Liver	HCC	RNA splicing	313/7958	434/18723	1.36e-36	1.73e-33	313
GO:000037522	Liver	HCC	RNA splicing, via transesterification reactions	228/7958	324/18723	1.47e-24	4.06e-22	228
GO:000037722	Liver	HCC	RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	224/7958	320/18723	1.16e-23	2.62e-21	224
GO:000039822	Liver	HCC	mRNA splicing, via spliceosome	224/7958	320/18723	1.16e-23	2.62e-21	224
GO:190331121	Liver	HCC	regulation of mRNA metabolic process	205/7958	288/18723	3.38e-23	6.90e-21	205
GO:004348422	Liver	HCC	regulation of RNA splicing	113/7958	148/18723	4.32e-17	4.15e-15	113
GO:005068421	Liver	HCC	regulation of mRNA processing	106/7958	137/18723	7.64e-17	7.12e-15	106

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Enriched KEGG pathways.

Pathway ID	Tissue	Disease Stage	Description	Gene Ratio	Bg Ratio	pvalue	p.adjust	qvalue	Count
hsa030152	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030153	Colorectum	FAP	mRNA surveillance pathway	26/1404	97/8465	7.11e-03	2.64e-02	1.60e-02	26
hsa030159	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa0301514	Esophagus	HGIN	mRNA surveillance pathway	30/1383	97/8465	2.48e-04	2.69e-03	2.14e-03	30
hsa0301524	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa0301534	Esophagus	ESCC	mRNA surveillance pathway	72/4205	97/8465	6.12e-07	4.10e-06	2.10e-06	72
hsa030154	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0301511	Liver	Cirrhotic	mRNA surveillance pathway	46/2530	97/8465	1.92e-04	1.30e-03	8.03e-04	46
hsa0301521	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa0301531	Liver	HCC	mRNA surveillance pathway	66/4020	97/8465	3.16e-05	1.88e-04	1.04e-04	66
hsa030158	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301513	Oral cavity	OSCC	mRNA surveillance pathway	75/3704	97/8465	1.30e-11	2.01e-10	1.02e-10	75
hsa0301523	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50
hsa0301533	Oral cavity	LP	mRNA surveillance pathway	50/2418	97/8465	1.39e-06	1.50e-05	9.66e-06	50

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Cell-cell communication analysis

Identification of potential cell-cell interactions between two cell types and their ligand-receptor pairs for different disease states

Ligand

Receptor

LRpair

Pathway

Tissue

Disease Stage

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Single-cell gene regulatory network inference analysis

Find out the significant the regulons (TFs) and the target genes of each regulon across cell types for different disease states

Cell Type

Tissue

Disease Stage

Target Gene

RSS

Regulon Activity

∗The dot plots of a searched regulon are shown for all cell subpopulations in each disease state of each tissue based on the regulon specific score inferred using pySCENIC and by calculating the average expression.

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Somatic mutation of malignant transformation related genes

Annotation of somatic variants for genes involved in malignant transformation

Hugo Symbol

Variant Class

Variant Classification

dbSNP RS

HGVSc

HGVSp

HGVSp Short

SWISSPROT

BIOTYPE

SIFT

PolyPhen

Tumor Sample Barcode

Tissue

Histology

Sex

Age

Stage

Therapy Types

Drugs

Outcome

DAZAP1

SNV

Missense_Mutation

rs770991534

c.320N>A

p.Ser107Asn

p.S107N

Q96EP5

protein_coding

tolerated(0.28)

benign(0.009)

TCGA-AC-A23H-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Unknown

DAZAP1

insertion

Frame_Shift_Ins

novel

c.801_802insACAGCTGGTGGACACGGCGCCAACC

p.Ser268ThrfsTer167

p.S268Tfs*167

Q96EP5

protein_coding

TCGA-A8-A097-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

tamoxiphen

DAZAP1

insertion

Nonsense_Mutation

novel

c.208_209insTCTAAGGCGAGCGCTGTCTTGATCCTGAATGTTTTCTCATTGAATC

p.Ser70IlefsTer2

p.S70Ifs*2

Q96EP5

protein_coding

TCGA-AR-A0TY-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unspecific

Paclitaxel

DAZAP1

deletion

Frame_Shift_Del

c.764delN

p.Pro257ArgfsTer78

p.P257Rfs*78

Q96EP5

protein_coding

TCGA-BH-A0HA-01

Breast

breast invasive carcinoma

Female

<65

I/II

Unknown

DAZAP1

deletion

Frame_Shift_Del

c.764delN

p.Pro257ArgfsTer78

p.P257Rfs*78

Q96EP5

protein_coding

TCGA-E2-A154-01

Breast

breast invasive carcinoma

Female

>=65

I/II

Hormone Therapy

arimidex

DAZAP1

SNV

Missense_Mutation

rs771366198

c.853N>A

p.Gly285Ser

p.G285S

Q96EP5

protein_coding

tolerated(0.24)

benign(0.001)

TCGA-2W-A8YY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DAZAP1

SNV

Missense_Mutation

novel

c.352N>A

p.Gly118Ser

p.G118S

Q96EP5

protein_coding

deleterious(0)

probably_damaging(1)

TCGA-C5-A8XK-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DAZAP1

SNV

Missense_Mutation

rs771366198

c.853N>A

p.Gly285Ser

p.G285S

Q96EP5

protein_coding

tolerated(0.24)

benign(0.001)

TCGA-EK-A2RJ-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Unknown

DAZAP1

SNV

Missense_Mutation

novel

c.57N>T

p.Trp19Cys

p.W19C

Q96EP5

protein_coding

deleterious(0)

probably_damaging(0.999)

TCGA-VS-A9UY-01

Cervix

cervical & endocervical cancer

Female

<65

I/II

Chemotherapy

cisplatin

DAZAP1

SNV

Missense_Mutation

c.920C>T

p.Pro307Leu

p.P307L

Q96EP5

protein_coding

deleterious(0.03)

benign(0.06)

TCGA-DM-A0X9-01

Colorectum

colon adenocarcinoma

Female

>=65

I/II

Unknown

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Related drugs of malignant transformation related genes

Identification of chemicals and drugs interact with genes involved in malignant transfromation

(DGIdb 4.0)

Entrez ID

Symbol

Category

Interaction Types

Drug Claim Name

Drug Name

PMIDs

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